Alpha-3 beta-4 nicotinic acetylcholine receptor (α3β4 nAChR) (α3β4 nAChR)

The alpha-3 beta-4 nicotinic acetylcholine receptor (α3β4 nAChR) is a subtype of pentameric ligand-gated ion channels composed of α3 and β4 subunits [PMID: 25839611]. It is predominantly localized in the autonomic ganglia, adrenal medulla, and the medial habenula-interpeduncular nucleus (MHb-IPN) axis of the brain [PMID: 30639451]. In the peripheral nervous system, it facilitates ganglionic transmission, while in the central nervous system, it acts as a key regulator of the cholinergic anti-reward system that limits excessive drug intake [PMID: 26851517]. Genetic polymorphisms in the CHRNA3/A5/B4 gene cluster are highly correlated with nicotine consumption and tobacco-related diseases such as lung cancer [PMID: 18385676]. Therapeutic interest in α3β4 nAChRs focuses on treating substance use disorders, with compounds like 18-methoxycoronaridine showing promise in reducing self-administration of morphine and cocaine [PMID: 21840572]. However, drug development is challenged by the need for selectivity to avoid off-target autonomic effects such as cardiovascular instability and gastrointestinal distress [PMID: 25839611].

Other names

CHRNA3-CHRNB4 receptorGanglionic nicotinic acetylcholine receptorNeuronal acetylcholine receptor subunit alpha-3/beta-4 complexα3β4-containing nAChR

Agonism, partial agonism, or non-competitive antagonism of the pentameric cation channel, modulating the influx of sodium, potassium, and calcium ions across the cell membrane.